Synthesis and in vitro degradation of testosterone-lipid conjugates.

Testosterone-lipid conjugates were obtained by covalent binding of the drug to 1,3-dipalmitoylglycerol via succinic acid to 4-(1,3-dipalmitoyl-2-glyceryl)butyric acid and to 3-palmitoyloxy-2-palmitoyloxmethylpropionic acid. In contrast to the corresponding bis-deacyl derivatives, the lipids were not significantly hydrolyzed in aqueous buffers and in plasma. Incubation with pancreatic lipase yielded primarily the bis-deacyl compounds, which are comparable to monoglycerides, and subsequently slowly liberated testosterone. It is concluded that the lipid conjugates are substrates for pancreatic lipase. However, the drug was released very slowly due to steric hindrance.